The secondary immune response, called immunologic memory, is the ability to mount a more vigorous response to a second encounter with antigen. Regardless of the fact that this is an extremely critical phenomenon in both infectious and degenerative diseases, little is known about immunologic memory. Currently we believe that memory is carried by a special population of long-lived small lymphocytes, and the duration of memory is dependent upon both the rate of formation of new memory cells and their biological half-life. In the intact animal it is difficult to separate these two events, consequently I propose to study memory cells in adoptive recipients. Using such a model I have found that, in the absence of antigen, the capacity of transferred memory cells to produce a secondary response declines surprisingly fast. Therefore, the initial aims of this research proposal are: (1) to determine accurately in adoptive recipients the functional half-life of immunologic memory cells when antigen is absent; (2) to demonstrate whether antigen can potentiate the survival of memory without recruiting new memory cells; (3) to study the mechanisms by which antigen modulates immunologic memory; and (4) to identify more precisely the role of different memory cells in this model. After establishing the system, I then intend to investigate how antigen and immunosuppressive agents can be used to modify immunologic memory.